tbuckley/cabot-search huggingface dataset:
Role of HNF4alpha-cMyc interaction in liver regeneration and recovery after acetaminophen-induced acute liver injury
Authors: Manasi Kotulkar, Diego Paine-Cabrera, Sarah Abernathy, Dakota R. Robarts, Wendena S. Parkes, Kristi Lin-Rahardja, September Numata, Margitta Lebofsky, Hartmut Jaeschke, Udayan Apte
Journal: Hepatology (2023)

Background and Aims: Overdose of acetaminophen (APAP) is the major cause of acute liver failure in the western world. We report a novel signaling interaction between hepatocyte nuclear factor 4 alpha (HNF4α) cMyc and nuclear factor erythroid 2–related factor 2 (Nrf2) during liver injury and regeneration after APAP overdose. Approach and Results: APAP-induced liver injury and regeneration were studied in male C57BL/6J (WT) mice, hepatocyte-specific HNF4α knockout mice (HNF4α-KO), and HNF4α-cMyc double knockout mice (DKO). C57BL/6J mice treated with 300 mg/kg maintained nuclear HNF4α expression and exhibited liver regeneration, resulting in recovery. However, treatment with 600-mg/kg APAP, where liver regeneration was inhibited and recovery was delayed, showed a rapid decline in HNF4α expression. HNF4α-KO mice developed significantly higher liver injury due to delayed glutathione recovery after APAP overdose. HNF4α-KO mice also exhibited significant induction of cMyc, and the deletion of cMyc in HNF4α-KO mice (DKO mice) reduced the APAP-induced liver injury. The DKO mice had significantly faster glutathione replenishment due to rapid induction in Gclc and Gclm genes. Coimmunoprecipitation and ChIP analyses revealed that HNF4α interacts with Nrf2 and affects its DNA binding. Furthermore, DKO mice showed significantly faster initiation of cell proliferation resulting in rapid liver regeneration and recovery. Conclusions: These data show that HNF4α interacts with Nrf2 and promotes glutathione replenishment aiding in recovery from APAP-induced liver injury, a process inhibited by cMyc. These studies indicate that maintaining the HNF4α function is critical for regeneration and recovery after APAP overdose.
Long noncoding RNA HIKER regulates erythropoiesis in Monge’s disease via CSNK2B
Authors: Priti Azad, Dan Zhou, Hung-Chi Tu, Francisco C. Villafuerte, David Traver, Tariq M. Rana, Gabriel G. Haddad
Journal: Journal of Clinical Investigation (2023)

Excessive Erythrocytosis (EE) is a major hallmark of patients suffering from chronic mountain sickness (CMS, Monge's disease) and is responsible for major morbidity and even mortality in early adulthood. We took advantage of unique populations, one living at high altitude (Peru) showing EE, while another population, at the same altitude and region, shows no evidence of EE (non-CMS). Through RNA-seq, we identified and validated the function of a group of long non-coding RNA (lncRNAs) that regulate erythropoiesis in Monge's disease but not in the non-CMS population. Among these lncRNAs is HIKER (Hypoxia Induced Kinase-mediated Erythropoietic Regulator)/LINC02228 which we showed plays a critical role in erythropoiesis in CMS cells. Under hypoxia, HIKER modulated CSNK2B (the regulatory subunit of Casein kinase 2). A down-regulation of HIKER down-regulated CSNK2B, remarkably reducing erythropoiesis (<70% reduction of BFUs); furthermore, an up-regulation of CSNK2B on the background of HIKER down-regulation rescued erythropoiesis defects. Pharmacologic inhibition of CSNK2B drastically reduced erythroid colonies (50-75% reduction in BFU colonies) and knock-down of CSNK2B in zebrafish lead to a defect in hemoglobinization (<97% morphants show reduction in hemoglobin levels). We conclude that HIKER regulates erythropoiesis in Monge's disease and acts through at least one specific target, CSNK2B, a casein kinase.
Postcolonoscopy Colorectal Cancer as a Quality Metric—Identifying Opportunities to Improve Outcomes
Authors: Abraham Segura, Shivan J. Mehta
Journal: JAMA Network Open (2023)

Charles J. Kahi, MD, MSc; Laura J. Myers, PhD; Patrick O. Monahan, PhD; Barry C. Barker, MA; Timothy E. Stump, MA; Thomas F. Imperiale, MD
Mortality After Postcolonoscopy Colorectal Cancer in the Veterans Affairs Health Care System
Authors: Charles J. Kahi, Laura J. Myers, Patrick O. Monahan, Barry C. Barker, Timothy E. Stump, Thomas F. Imperiale
Journal: JAMA Network Open (2023)

Importance Postcolonoscopy colorectal cancer (PCCRC) refers to colorectal cancer (CRC) diagnosed after a colonoscopy in which no cancer was found and is reflective of colonoscopy quality at the individual and system levels. Colonoscopy is widely performed in the Veterans Affairs (VA) health care system, but the prevalence of PCCRC and its associated mortality are unknown. Objective To examine PCCRC prevalence and its all-cause mortality (ACM) and CRC-specific mortality (CSM) within the VA health care system. Design, Setting, and Participants This retrospective cohort study used VA-Medicare administrative data to identify 29 877 veterans aged 50 to 85 years with newly diagnosed CRC between January 1, 2003, and December 31, 2013. Patients whose colonoscopy occurred less than 6 months before CRC diagnosis with no other colonoscopy within the previous 36 months were categorized as having detected CRC (DCRC). Those who had a colonoscopy that did not detect CRC between 6 and 36 months before CRC diagnosis were categorized as having postcolonoscopy CRC (PCCRC-3y). A third group included patients with CRC and no colonoscopy within the prior 36 months. The final analysis of the data was performed in September 2022. Exposures Prior receipt of colonoscopy. Main Outcomes and Measures Cox proportional hazards regression (with censoring, last follow-up December 31, 2018) analyses were conducted to compare PCCRC-3y and DCRC for 5-year ACM and CSM after CRC diagnosis. Results Of 29 877 patients with CRC (median [IQR] age, 67 [60-75] years; 29 353 [98%] male; 5284 [18%] Black, 23 971 [80%] White, and 622 [2%] other), 1785 (6%) were classified as having PCCRC-3y and 21 811 (73%) as having DCRC. The 5-year ACM rates were 46% vs 42% for patients with PCCRC-3y vs patients with DCRC. The 5-year CSM rates were 26% vs 25% for patients with PCCRC-3y vs patients with DCRC. In multivariable Cox proportional hazards regression analysis, there was no significant difference in ACM and CSM between patients with PCCRC-3y (adjusted hazard ratio [aHR], 1.04; 95% CI, 0.98-1.11; P = .18) and patients with DCRC (aHR, 1.04; 95% CI, 0.95-1.13; P = .42). However, compared with patients with DCRC, patients with no prior colonoscopy had significantly higher ACM (aHR, 1.76; 95% CI, 1.70-1.82; P &amp;amp;lt; .001) and CSM (aHR, 2.22; 95% CI, 2.12-2.32; P &amp;amp;lt; .001). Compared with patients with DCRC, patients with PCCRC-3y had significantly lower odds of having undergone colonoscopy performed by a gastroenterologist (odds ratio, 0.48; 95% CI, 0.43-0.53; P &amp;amp;lt; .001). Conclusions and Relevance This study found that PCCRC-3y constituted 6% of CRCs in the VA system, which is similar to other settings. Compared with patients with CRC detected by colonoscopy, those with PCCRC-3y have comparable ACM and CSM.
Association of Polycystic Ovary Syndrome With Pancreatic Cancer
Authors: Gabriel Levin, Raanan Meyer
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Maternal-infant antibiotic resistance genes transference: what do we know?
Authors: Anna Samarra, Maria Esteban-Torres, Raul Cabrera-Rubio, Manuel Bernabeu, Silvia Arboleya, Miguel Gueimonde, Maria Carmen Collado
Journal: Gut Microbes (2023)

Resistance to antibiotics is becoming a worldwide threat as infections caused by multidrug-resistant pathogenic microorganisms can overcome antibiotic treatments and spread quickly in the population. In the context of early life, newborns are at increased risk as their immune system is still under development, so infections and acquisition of resistance during childhood have short- and long-term consequences for the health. The moment of birth is the first exposure of infants to possible antibiotic-resistant microorganisms that may colonize their gut and other body sites. Different factors including mode of delivery, previous antibiotic exposure of the mother, gestational age and consumption of antibiotics in early-life have been described to modulate the neonate's microbiota, and thus, the resistome. Other factors, such as lactation, also impact the establishment and development of gut microbiota, but little is known about the role of breastmilk in transferring Antibiotic Resistant Genes (ARG). A deeper understanding of vertical transmission of antibiotic resistance from mothers to their offspring is necessary to determine the most effective strategies for reducing antibiotic resistance in the early life. In this review, we aim to present the current perspective on antibiotic resistances in mother-infant dyads, as well as a new insight on the study of the human gut and breastmilk resistome, and current strategies to overcome this public health problem, toward highlighting the gaps of knowledge that still need to be closed.
Intestinal mucin-type <i>O</i> -glycans: the major players in the host-bacteria-rotavirus interactions
Authors: S.A. Raev, J.O. Amimo, L.J. Saif, A.N. Vlasova
Journal: Gut Microbes (2023)

Rotavirus (RV) causes severe diarrhea in young children and animals worldwide. Several glycans terminating in sialic acids (SAs) and histo-blood group antigens (HBGAs) on intestinal epithelial cell (IEC) surface have been recognized to act as attachment sites for RV. IECs are protected by the double layer of mucus of which O-glycans (including HBGAs and SAs) are a major organic component. Luminal mucins, as well as bacterial glycans, can act as decoy molecules removing RV particles from the gut. The composition of the intestinal mucus is regulated by complex O-glycan-specific interactions among the gut microbiota, RV and the host. In this review, we highlight O-glycan-mediated interactions within the intestinal lumen prior to RV attachment to IECs. A better understanding of the role of mucus is essential for the development of alternative therapeutic tools including the use of pre- and probiotics to control RV infection.
In vivo evolution to echinocandin resistance and increasing clonal heterogeneity in Candida auris during a difficult-to-control hospital outbreak, Italy, 2019 to 2022
Authors: Giulia Codda, Edward Willison, Laura Magnasco, Paola Morici, Daniele Roberto Giacobbe, Antonella Mencacci, Daniele Marini, Malgorzata Mikulska, Matteo Bassetti, Anna Marchese, Vincenzo Di Pilato
Journal: Eurosurveillance (2023)

A difficult-to-control outbreak of Candida auris is ongoing in a large tertiary care hospital in Liguria, Italy, where it first emerged in 2019. In a retrospective analysis, 503 cases of C. auris carriage or infection were observed between July 2019 and December 2022. Genomic surveillance identified putative cases that no longer occurred as part of one defined outbreak and the emergence of echinocandin (pandrug) resistance following independent selection of FKS1S639F and FKS1F635Y mutants upon prolonged exposure to caspofungin and/or anidulafungin.
Glucose‐Responsive Antioxidant Hydrogel Accelerates Diabetic Wound Healing
Authors: Fang Chen, Jianghui Qin, Pingli Wu, Wenshan Gao, Guoming Sun
Journal: Advanced Healthcare Materials (2023)

Diabetic complications can be ameliorated by inhibiting excessive oxidative stress with antioxidants. To enhance therapeutic intervention, it is crucial to develop intelligent scaffolds for efficient delivery of antioxidants to diabetic wounds. This study introduces reversible boronic bonds to create an intelligent antioxidant hydrogel scaffold. This study modifies gelatin methacryloyl (GelMA) with 4-carboxyphenyboronic acid (CPBA) to synthesize a derivative of GelMA (GelMA-CPBA), and then photo cross-links GelMA-CPBA with (−)-epigallocatechin-3-gallate (EGCG) to form GelMA-CPBA/EGCG (GMPE) hydrogel. The GMPE hydrogel responds to changes in glucose levels, and more EGCG is released as glucose level increases due to the dissociation of boronic ester bonds. The GMPE hydrogel shows good biocompatibility and biodegradability, and its mechanical property is similar to that of the skin tissue. Both in vitro and in vivo results demonstrate that the GMPE hydrogel scaffolds effectively eliminate reactive oxygen species (ROS), reduce the inflammation, and promote angiogenesis, thereby improve collagen deposition and tissue remodeling during diabetic wound healing. This strategy offers new insight into glucose-responsive scaffolds, and this responsive antioxidan hydrogel scaffold holds great potential for the treatment of chronic diabetic wounds.
Photoprotection and skin cancer education: the experiences of renal transplant recipients, a qualitative study – why the ‘personal touch’ is important
Authors: Laoise Griffin, Pauline O’Reilly, Marcus Murphy, Gemma Prendergast, Emily Pender, Olga Tummon, Matthew Griffin, Mary Laing
Journal: British Journal of Dermatology (2023)

Our qualitative study of the skin cancer information delivered to renal transplant recipients (RTRs) highlighted that we must find the optimum time when things are settled for patients to absorb this information. Knowing and trusting the person delivering the information was welcomed by participants and more likely to influence behaviour, as was the healthcare professional who took time to consider the individuality of recipients. Knowledge gaps have been uncovered and require consideration, including a predominant concern of melanoma rather than squamous cell carcinoma, and a reliance on sunscreen and not other sun protective measures. Renal colleagues are highly considered by RTRs and well placed to deliver interventions
Ventilation Improvements Among K–12 Public School Districts — United States, August–December 2022
Authors: Miguella Mark-Carew, Gloria Kang, Sanjana Pampati, Kenneth R. Mead, Stephen B. Martin, Lisa C. Barrios
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Improving ventilation has been one of several COVID-19 prevention strategies implemented by kindergarten through grade 12 (K-12) schools to stay open for safe in-person learning. Because transmission of SARS-CoV-2 occurs through inhalation of infectious viral particles, it is important to reduce the concentration of and exposure time to infectious aerosols (1-3). CDC examined reported ventilation improvement strategies among U.S. K-12 public school districts using telephone survey data collected during August-December 2022. Maintaining continuous airflow through school buildings during active hours was the most frequently reported strategy by school districts (50.7%); 33.9% of school districts reported replacement or upgrade of heating, ventilation, and air conditioning (HVAC) systems; 28.0% reported installation or use of in-room air cleaners with high-efficiency particulate air (HEPA) filters; and 8.2% reported installation of ultraviolet (UV) germicidal irradiation (UVGI) devices, which use UV light to kill airborne pathogens, including bacteria and viruses. School districts in National Center for Education Statistics (NCES) city locales, the West U.S. Census Bureau region, and those designated by U.S. Census Bureau Small Area Income Poverty Estimates (SAIPE) as high-poverty districts reported the highest percentages of HVAC system upgrades and HEPA-filtered in-room air cleaner use, although 28%-60% of all responses were unknown or missing. Federal funding remains available to school districts to support ventilation improvements. Public health departments can encourage K-12 school officials to use available funding to improve ventilation and help reduce transmission of respiratory diseases in K-12 settings.
Alemtuzumab in relapsed immune severe aplastic anemia: Long‐term results of a phase II study
Authors: Nidhi Aggarwal, Ash Lee Manley, Ruba Shalhoub, Jibran Durrani, Olga Rios, Jennifer Lotter, Bhavisha A. Patel, Colin O. Wu, Neal S. Young, Emma M. Groarke
Journal: American Journal of Hematology (2023)

Abstract Immune severe aplastic anemia (SAA) is characterized by pancytopenia and immune‐mediated bone marrow destruction. SAA may be treated with hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). However, 30% of patients treated with IST relapse. We previously reported a clinical trial of alemtuzumab in which more than half of 25 relapsed SAA patients (56%) responded hematologically. Here, we present long‐term results of a total of 42 patients. Participants with SAA who had previously completed antithymocyte globulin (ATG)‐based IST, but had relapsed, were enrolled on this study. Alemtuzumab was administered intravenously (IV) ( n = 28) or subcutaneously (SC) ( n = 14). The primary endpoint was hematologic response at 6 months. Secondary endpoints included relapse, clonal evolution, and survival. This trial was registered at clinicaltrials.gov (NCT00195624). Patients were enrolled over 9 years, with median follow‐up of 6 years. Median age was 32 years, with 57% being female. At 6 months, 18 patients (43%) achieved response; 15 (54%) of those who received IV compared with 3 (21%) who received SC therapy. Six patients (14%) had durable long‐term response without need for subsequent AA‐directed therapy or HSCT at last follow‐up. Nine patients had clonal evolution, with high‐risk evolution occurring in 6. Overall survival was 67% at median follow‐up of 6 years. Prolonged iatrogenic immunosuppression was observed as long as 2 years after alemtuzumab administration. Alemtuzumab induces responses in relapsed SAA, some of which are durable long‐term. However, immunosuppression can persist for years, requiring long‐term monitoring.
Risk of Death in Patients Hospitalized for COVID-19 vs Seasonal Influenza in Fall-Winter 2022-2023
Authors: Yan Xie, Taeyoung Choi, Ziyad Al-Aly
Journal: JAMA (2023)

This study uses data from the US Department of Veterans Affairs to assess whether SARS-CoV-2 remains associated with higher risk of death compared with seasonal influenza in fall-winter 2022-2023.
Widespread Community Transmission of Hepatitis A Virus Following an Outbreak at a Local Restaurant — Virginia, September 2021–September 2022
Authors: Meagan J. Helmick, Cynthia B. Morrow, J. Hope White, Paige Bordwine
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Hepatitis A is a vaccine-preventable liver infection caused by the hepatitis A virus (HAV); it is transmitted through ingestion of food or drink that has been contaminated by small amounts of infected stool, or through direct contact, including sexual contact, with a person who is infected (1). After years of historically low rates of hepatitis A in the United States, the incidence began increasing in 2016, with outbreaks characterized by person-to-person HAV transmission among persons who use drugs, persons experiencing homelessness, and men who have sex with men (2,3). As of September 2022, 13 states were experiencing outbreaks, including Virginia (3). In September 2021, the Roanoke City and Alleghany Health Districts (RCAHD) in southwestern Virginia investigated an outbreak of hepatitis A. The outbreak, which resulted in 51 cases, 31 hospitalizations, and three deaths, was associated with a food handler who was infected. After the outbreak, the community experienced ongoing person-to-person transmission of HAV, predominantly among persons who use injection drugs. As of September 30, 2022,* an additional 98 cases had been reported to RCAHD. The initial outbreak and community transmission have exceeded US$3 million in estimated direct costs (4,5). This report describes the initial outbreak and the ongoing community transmission of HAV. Increasing vaccination coverage among persons with risk factors for hepatitis A infection is important, including among those who use drugs. Strengthening community partnerships between public health officials and organizations that employ persons with risk factors for acquisition of HAV could help to prevent infections and outbreaks.
Financial Toxicity Among Caregivers of Patients With Cancer—An Increasing Problem Requiring Novel Solutions
Authors: Ayush Peddireddi, Emeline M. Aviki
Journal: JAMA Network Open (2023)

Lauren V. Ghazal, PhD, FNP-BC; Paul Abrahamse, MA; Kevin C. Ward, PhD; Arden M. Morris, MD, MPH; Sarah T. Hawley, PhD; Christine M. Veenstra, MD, MSHP
Meta-analysis reveals <i>Helicobacter pylori</i> mutual exclusivity and reproducible gastric microbiome alterations during gastric carcinoma progression
Authors: Yan Li, Yichen Hu, Xiang Zhan, Ying Song, Meng Xu, Shijie Wang, Xiaochang Huang, Zhenjiang Zech Xu
Journal: Gut Microbes (2023)

Accumulating evidence shows that the gastric bacterial community may contribute to the development of gastric cancer (GC). However, the reported alterations of gastric microbiota were not always consistent among the literature. To assess reproducible signals in gastric microbiota during the progression of GC across studies, we performed a meta-analysis of nine publicly available 16S datasets with standard tools of the state-of-the-art. Despite study-specific batch effect, significant changes in the composition of the gastric microbiome were found during the progression of gastric carcinogenesis, especially when the Helicobacter pylori (HP) reads were removed from analyses to mitigate its compositional effect as they accounted for extremely large proportions of sequencing depths in many gastric samples. Differential microbes, including Fusobacterium, Leptotrichia, and several lactic acid bacteria such as Bifidobacterium, Lactobacillus, and Streptococcus anginosus, which were frequently and significantly enriched in GC patients compared with gastritis across studies, had good discriminatory capacity to distinguish GC samples from gastritis. Oral microbes were significantly enriched in GC compared to precancerous stages. Intriguingly, we observed mutual exclusivity of different HP species across studies. In addition, the comparison between gastric fluid and mucosal microbiome suggested their convergent dysbiosis during gastric disease progression. Taken together, our systematic analysis identified novel and consistent microbial patterns in gastric carcinogenesis.